The document discusses the role of glial cells, particularly astrocytes, as active modulators within neural networks, emphasizing the importance of the glia/neuron ratio in understanding brain function and evolution. It also highlights the significance of sleep for memory and cognitive functions, presenting various theories on sleep's functionality and its relationship with synaptic homeostasis. The research suggests that astrocytes have a fundamental role in synaptic modulation and sleep regulation, raising questions about their intrinsic characteristics and contributions to complex neural networks.

1. Glial cells and astrocytes:
neural network modulators?
Hugo Trad & Stephen Larroque
2 Nov 2015

2. Glia/Neuron ratio
• Glia not just a « glue », lots of different
functions
• Friede (1954) : Glial index, or glia/neurons
(G/N) ratio
• How does this ratio vary across species, and
to what extent this variation can be
informative of glia’s function ?
2
(Herculano-Houzel, 2014)

3. G/N varies with brain size?
3
(Herculano-Houzel, 2014)

4. G/N varies with brain size?
4
(Herculano-Houzel, 2014)

5. G/N varies with brain size?
5
(Herculano-Houzel, 2014)

6. G/N varies with neuronal density
6
(Herculano-Houzel, 2014)

7. G/N varies with neuronal density
7
(Herculano-Houzel, 2014)

8. Varies with neuronal density?
• Why ?
– Metabolic argument : larger neurons because of
smaller neuronal density (= metabolic cost?)
8
(Herculano-Houzel, 2014)

9. Varies with neuronal density?
• Why ?
– Metabolic argument : larger neurons because of
smaller neuronal density (= metabolic cost?)
9
(Herculano-Houzel, 2014)

10. Varies with neuronal density?
• Why ?
– Developmental argument : glia can proliferate
during postnatal development
– Glia : small size variations
and uniformly distributed
(contrary to neurons)
→ G/N vary with neuronal
density (not glial density)
– Consistent with data !
10
(Herculano-Houzel, 2014)

11. Implications of G/N ratio
• Uniform variation → highly conservated
throughout evolution
• Suggests glial cells perform fundamental role,
since they can hardly be altered
• May favor sparse coding
• Human exception : larger and more complex
astrocytes. Why ?
– Brain size vs intrinsic properties of human astrocytes ?
– Core to human cognition ?
11
(Herculano-Houzel, 2014)

12. Why is sleep important?
• Essential for memory and cognitive functions
• Universal for all animals with a brain (mammals, birds,
insects?, etc.)
• Necessary, else death is guaranteed
• Precise physiological (REM/NREM, slow waves) or
behavioral (no response to stimuli) definitions
• Compensation after deprivation (more frequent slow waves)
• Questions :
– What functionality ?
– How it works ? 12

13. Sleep functionality: theories
• Synaptic homeostasis (SHY) (Tononi & Cirelli,
2003) : wake LTP-potentiated synapses weights
are normalized during sleep for efficiency
• Memory trace replay (Lee & Wilson,2002) :
memories are consolidated by offline
reactivation during sleep
=> Sleep = regulation of plasticity ?
=> Contradictory or complementary theories?
13

14. Local synaptic modulation
14
• 2 pathways for local synaptic modulation by astrocytes :
(2B) A1 pathway is tonically activated to clean neurotransmitters,
While phasic A1 activation can regulate depending on synaptic activity
(Fellin et al, 2014)

15. Up-down states modulation
15
• Slow waves reduction in sleep-deprived dnSNARE mice can be
explained by the modulation of up-down states probabilities :
Deprived dnSNARE mice cannot compensate !
(Fellin et al, 2009)

16. Take home message
• Astrocytes :
– Active synaptic modulators (not just passive regulators)
similar to neurons gatekeepers (synaptic gating)
– Highly conservated throughout evolution = essential role
– Essential (core?) for sleep (and thus memory) functions
• Questions :
– Characteristics intrinsic or due to neural environment ?
– Astrocytes participate in the formation of complex neural
networks ? Do evolved astrocytes allow to better learn ?
16

17. – The Glia/Neuron Ratio, Herculano-Houzel, 2014, Glia, 62(9), 1377-1391.
– Astrocyte regulation of sleep circuits: experimental and modeling
perspectives, Fellin et al, Frontiers in Computational Neuroscience, 2014
– Time to be SHY? Some comments on sleep and synaptic homeostasis,
Tononi & Cirelli, 2012, Neural plasticity.
– Astrocytes drive neural network synchrony, Levine-Small & Guebeli &
Goddard & Yang & Chuong & Chow & Egert, 2012, In MEA Meeting 2012(p.
30).
– Memory of sequential experience in the hippocampus during slow wave
sleep, Lee & Wilson, 2002, Neuron, 36(6), 1183-1194.
– Reverse replay of behavioural sequences in hippocampal place cells
during the awake state, Foster & Wilson, 2006, Nature, 440(7084), 680-
683.
References
slideshare.net/LRQ3000

18. Thank you!
slideshare.net/LRQ3000

19. Bonus Slides

20. Network synchrony modulation
23
Local phasic ATP/Adn modulation may promote global synchrony :
(Fellin et al, 2014)

21. Sleep-deprived dnSNARE mice
24
• Sleep-deprived dnSNARE mice have difficulties to compensate
when under high homeostatic sleep pressure :
Deprived dnSNARE mice have reduced compensation !
(Fellin et al, 2009)

22. Bistable neurons, synaptic gating
25
• Bistable neurons can switch between two states : Up and Down
• Allow to create selective inhibition (aka : synaptic gating)
• A third neuron (or astrocyte?) can modulate this gating : the
gatekeeper

23. Up and down state in one neuron
26
• Up-state = depolarized ; Down-state = hyperpolarized (close to
membrane potential).
• Change neuron’s dynamics ; Up needs balanced excitation and
inhibition ? (Wilson & Cowan 1972)
• Can switch state without triggering a spike
DownDownUpUp

24. Up and down states
27
• Up and down states in dnSNARE mice (in-vivo patch-clamp
recordings from pyramidal neurons in somato-sensory cortex) :
(Fellin et al, 2009)

25. Neural oscillations
28
• Oscillation = rythmic pattern of activation of a
single neuron or a network

26. THE END